What is Heart Transplantation Allograft Vasculopathy?
Over 5.1 million people in the United States live with chronic heart failure, a condition that’s a leading cause of hospitalization amongst those over 65 years old. More than one million people are hospitalized annually due specifically to heart failure, contributing to Medicare spending over $17 billion each year on this health issue. While there have been advances in mechanical devices that help with circulation, a heart transplant is still the ultimate treatment for patients with severe heart failure whose symptoms can’t be controlled with medication.
The first human heart transplant was performed by Dr. Christiaan Barnard in 1967. Since then, the field has greatly evolved with the help of innovative technologies and a joint effort from various specialists. Today, more than 5,000 heart transplants are performed globally every year. But despite the progress, there are still challenges in this field.
One such challenge is Cardiac Allograft Vasculopathy (CAV), a potential long-term complication that can occur after a heart transplant. CAV is similar to a slow, ongoing rejection of the new heart and is one of the top three causes of death in the first year after a heart transplant. According to data from the International Society for Heart and Lung Transplantation, the rate of people developing CAV after a heart transplant was 8% after one year, 29% after five years, and 47% after ten years.
What Causes Heart Transplantation Allograft Vasculopathy?
Cardiac allograft vasculopathy (CAV) is a disease that affects all the arteries of a transplanted heart. Its causes are complex and mainly related to inflammation triggered by the body’s rejection of the transplanted heart, both at the cellular level and through antibodies. These antibodies, specifically called anti-HLA antibodies, react against the donor tissue.
The severity of the inflammation in this disease is often indicated by high levels of a substance in the blood called C-reactive protein. This is why an increase in this protein is often seen as a sign of CAV and possible failure of the transplanted heart.
Other factors that can contribute to this disease include high cholesterol levels, diabetes, high blood pressure, and infection with a virus known as Cytomegalovirus.
Risk Factors and Frequency for Heart Transplantation Allograft Vasculopathy
Cardiac allograft vasculopathy, or CAV, is a serious condition that is one of the three leading causes of death a year after a heart transplant. It’s estimated to be responsible for one in every eight deaths among patients who survive more than a year after their transplant. Based on data from the International Society for Heart and Lung Transplantation, the likelihood of surviving transplant patients developing CAV increases over time: 8% after one year, 29% after five years, and almost half (47%) after ten years. There are several factors that can increase this risk. Male donors and older donors have been linked to a higher risk of CAV. Also, younger recipients are found to be at higher risk.
- Cardiac allograft vasculopathy is one of the top three causes of death a year after heart transplant.
- It’s linked to 1 in 8 deaths among patients who live more than a year after their transplant.
- According to data, 8% develop CAV one year after transplant, 29% after five years, and 47% after ten years.
- Increased risk is associated with male donors and older donors.
- Younger patients receiving transplants are also at higher risk.
Signs and Symptoms of Heart Transplantation Allograft Vasculopathy
Heart transplant patients don’t typically feel chest pain related to heart disease because the new heart isn’t connected to the nerves that would normally send those signals. As a result, coronary artery disease (CAD) in these patients may reveal itself suddenly and unexpectedly. Signs could be as subtle as feeling unusually tired, shortness of breath, heart palpitations, stomach discomfort, or nausea.
If CAD isn’t detected until after it has caused heart failure or reduced the heart’s ability to pump blood efficiently, the patient’s outlook isn’t generally very good. In rare instances, the first indication of CAD might be sudden cardiac death. Because the typical signs and symptoms aren’t reliable in heart transplant patients, it’s crucial to monitor them closely for early clues of CAD.
- Unusual fatigue
- Shortness of breath
- Heart palpitations
- Stomach discomfort
- Nausea
Testing for Heart Transplantation Allograft Vasculopathy
People who have had a heart transplant should undergo regular screenings for a condition called cardiac allograft vasculopathy, as early detection can lead to a better outcome. In simpler terms, cardiac allograft vasculopathy is a condition where the blood vessels in the transplanted heart start to narrow and become blocked.
For the first 5 years after a heart transplant, a test called coronary angiography, which uses X-rays to see the heart’s blood vessels, should be carried out every one or two years, as long as kidney function is not seriously impaired. The health of the kidneys can be measured by something called the estimated glomerular filtration rate, which measures how well the kidneys are cleaning your blood. If the kidneys are significantly impaired, a different test called a dobutamine stress echocardiography, which uses sound waves to capture images of the heart, should be done every year to keep an eye out for reduced blood flow to the heart.
For patients who’ve been living with a transplanted heart for 5 years or more, if they are at low risk, they can continue having the dobutamine stress echocardiography test once a year. But if the condition of the heart’s blood vessels is getting worse, they might need to continue having annual coronary angiograms, again as long as the kidneys are functioning enough.
Coronary angiography should be done if there is a change in the patient’s health related to the heart, such as a drop in the left ventricular ejection fraction (a measure of how well the heart is pumping), which can’t be explained by acute rejection, which is when the body’s immune system attacks the new heart.
It’s worth noting that cardiac allograft vasculopathy makes the arteries in the heart narrow evenly, unlike another kind of heart disease called atherosclerosis, where the narrowing is uneven and easier to spot. Therefore, coronary angiography can sometimes underestimate how severe cardiac allograft vasculopathy is. Other techniques like intravascular ultrasound, which uses sound waves to see inside blood vessels, or optical coherence tomography, which uses light waves to produce high-resolution images of the blood vessels, may offer a more accurate assessment.
Once cardiac allograft vasculopathy has been diagnosed, echocardiograms (a type of ultrasound) should be done regularly to assess the left ventricular ejection fraction and monitor the function of the transplanted heart. Annual coronary angiograms can help decide whether percutaneous coronary interventions (procedures to improve blood flow to the heart) are needed, or in serious cases, whether a second heart transplant might be necessary. In any case, the presence of healthy heart blood vessels is always a good sign, predicting survival without further heart complications at two years.
Treatment Options for Heart Transplantation Allograft Vasculopathy
Certain medications called mTOR inhibitors, including everolimus and sirolimus, have been found to slow down or prevent the progression of cardiac allograft vasculopathy (a disease that affects the heart’s blood vessels after a transplant). However, they may cause side effects such as kidney problems and difficulty with wound healing which can limit their usage.
Another type of medication known as statins can reduce the chances of developing this condition after a heart transplant. They also address high levels of fat or cholesterol in the blood, a common problem in these patients. Therefore, it’s advised that all heart transplant patients use statins. Specifically, the statins named pravastatin and simvastatin have been found to enhance survival rates in these patients.
Intensifying the use of mTOR inhibitors in the short term can potentially halt or even reverse the progression of cardiac allograft vasculopathy. However, this needs further research for validation. Also, the associated risks of increasing immunosuppression, which includes higher likelihood of infections and cancer, might offset these potential benefits. Moreover, the use of an antibody called rituximab in a study involving 163 post-heart transplant patients did not appear effective, as the imaging tests revealed that the disease progressed more in patients given rituximab compared to those given a placebo.
If the disease is not widespread, a technique called percutaneous transluminal angioplasty can be used as a temporary remedy to treat specific lesions or damaged areas. However, the treated areas may narrow again. In such situations, a procedure called directional coronary atherectomy can be useful. Coronary artery bypass grafting, a form of heart surgery, has shown positive results in a selective group of patients in the medium term. But it does not eliminate the chances of disease progression and possible future need for non-surgical or surgical interventions. Currently, a second heart transplant remains the only definitive treatment for patients heavily affected by this condition.
What else can Heart Transplantation Allograft Vasculopathy be?
When a graft (or a transplanted organ) is not functioning properly, it can cause symptoms such as heart failure or abnormal heart rhythms. It’s important to figure out the root cause of these symptoms, which could be a variety of issues. For example, it could be due to blood vessels in the transplanted heart becoming narrow (a condition known as cardiac allograft vasculopathy). Alternatively, the body might be in the process of rejecting the transplant, or there might be a different issue causing problems.
To identify the problem, doctors might perform a biopsy to look for signs on the transplanted heart tissues. If cardiac allograft vasculopathy is suspected, a cardiac angiogram (a test that uses dye and special x rays to show the inside of heart’s blood vessels) may be conducted if kidney functionality allows. This test can show if the inside of blood vessels are abnormally narrow, which is a common sign of cardiac allograft vasculopathy. On the other hand, the presence of focal eccentric lesions, particularly in the proximal epicardial vessels, is more indicative of atherosclerosis, a heart disease characterized by thickening and hardening of the arteries. However, both conditions can exist simultaneously.
The following conditions could potentially cause graft dysfunction:
- Atherosclerosis
- Non-specific graft dysfunction
- Posttransplantation lymphoproliferative disorder
- Transplant rejection
What to expect with Heart Transplantation Allograft Vasculopathy
Cardiac allograft vasculopathy – a condition affecting the blood vessels in a transplanted heart – can make the outlook worse for patients after a heart transplant. This is typically used as an indicator to predict serious, non-deadly heart complications and considerable development of this condition within five years after the transplant. One key sign doctors look for is the blood vessel walls getting thicker by 0.5 mm or more in the first year after the transplant.
According to a 2019 report from the International Society for Heart and Lung Transplantation, the prevalence of this condition in patients after a heart transplant at 1, 5, and 10 years was 8%, 29%, and 47% respectively. This means that as time passes, the likelihood of developing this condition increases.
Possible Complications When Diagnosed with Heart Transplantation Allograft Vasculopathy
Cardiac graft disease could lead to a malfunction in the heart transplant, which may present as different symptoms like irregular heart rhythms. It might also cause severe conditions like acute or unexpected changes in heart ability to pump blood efficiently, chronic, or long-term heart failures, and in extremely serious instances, it could potentially lead to sudden death due to heart-related issues.
Common Symptoms:
- Irregular heart rhythms
- Acute, or unexpected, changes in heart’s ability to pump blood
- Chronic, or long-term, heart failure
- The potential for unexpected sudden death from heart-related issues
Preventing Heart Transplantation Allograft Vasculopathy
Correctly identifying and handling a condition called cardiac allograft vasculopathy can significantly affect the length and quality of life for someone who’s had a heart transplant. This condition involves blood vessel disease in the transplanted heart. It’s vital that healthcare providers fully explain the possible impact of cardiac allograft vasculopathy to patients after their heart transplant. This way, patients can make knowledgeable decisions about their treatment options.
